ASCO 2026：关键数据背后的创新趋势与价值判断

Heme: the CAR-T vs.bispecific sequencingquestion, plus in-vivoCAR-T arrives Heme:CAR-T vs Bispecific Sequencing is TheUnsolved Question Background:Myeloma and multiple aggressive B-cell lymphomas have two approved T-cell-redirecting classes;BsAbsand CAR Ts.The challenge has shifted fromselection to sequencing, as most patients need both. Pivotal trials generally exclude prior same-target exposure, so limitedhead-to-head or sequencing data exists,although real-world registries and guidelines are starting to fill the gap. Key ASCO 2026 data:•Primary Phase III data for the MajesTEC-9 trial(7507):Tecvayli(teclistamab; BCMA×CD3 bispecific) in r/r MM oMoves the bispecific earlier than its original 4L+ accelerated-approval setting and proves benefit there, but excluded prior BCMA exposure so the order againstCAR-T stays untested•Subgroup analysis of the Phase III CARTITUDE-4(7536):Carvykti(cilta-cel; BCMA CAR-T) in lenalidomide-refractoryMM oAlready-approved based on this trial; follow-up cements CAR-T's early-line position, but excluded prior CAR-T andbispecificslimits sequencing value•Updated Phase III follow-up of the Phase III SUNMO trial(7007):Lunsumio(mosunetuzumab; CD20×CD3 bispecific) plusPolivy(polatuzumabvedotin) in transplant-ineligible 2L+ r/r large B-cell lymphoma KOL sentiment at ASCO 2026:Across the sessions, KOLs kept returning to the same unresolved questions: how long a washout is needed between a bispecificandasubsequent CAR-T, whether de-escalated or fixed-duration bispecific dosing can preserve T-cell fitness, and how to choose when apatient needs rapid disease controlversus the deeper, one-time benefit of CAR-T. There was disagreement on whetherbispecificsshould ever precede CAR-T, and a recurring acknowledgement that real-world practice is being driven as much by access, fitness, and manufacturing logistics as by efficacy. Beyond ASCO 2026:In relapsed/refractory multiple myeloma, IMWG guidance and real-world data (US MM Immunotherapy Consortium) favor using CAR-T beforeBCMAbispecifics, since recent prior bispecific exposure is associated with reduced response and PFS to subsequent BCMA therapy, though no trialhas directly proventhe optimal order. The lymphoma picture stays more mixed, as registries such as DESCAR-T show prior bispecific bridging does notclearly compromise later CAR-T. Next steps:The field is now testing sequence directly through post-CAR-T bispecific trials in B-cell lymphoma, includingColumvias consolidation in R/R DLBCL afterCAR-T (PhII GLORY),Ordsponofollowing CAR-T in later-line≥3L B-cell malignancies (PhIELM-1), andEpkinlyin≥3L R/R LBCL including post-CAR-T patients (Ph I/IIEPCORE NHL-1). All position the bispecific after CAR-T, reinforcing the emerging CAR-T-first order, though they will refine post-CAR-T strategy rather than deliver adefinitive head-to-head answer.3 Heme:Next-Generation CAR-Ts, In VivoGeneration and Engineered Architectures Background:Conventional autologous CAR-T is potent but faces set-backs: a logistical one (apheresis, ex vivo manufacturing, lymphodepleting chemotherapy, high cost,restricted access) and a biological one (poor selectivity, persistence, and activity in solid tumors). ASCO 2026 showcased anapproach to each. In vivo generation tackles thelogistical barrier, making CAR-T inside the patient from a single off-the-shelf infusion, removing manufacturing, apheresis andlymphodepletion. Next-gen architectures (logic-gating, armoring, cytokine enhancement) tackle the biological barrier, engineering the cell for tumor selectivity, durable persistence, and solid-tumor activity. Key ASCO 2026 Data:•Updated Phase IinMMyCARtrial(7509):Kelonia'sKLN-1010 (in vivo BCMA CAR-T) in r/r multiple myeloma o100% ORR and MRD-negative at 1 month in all 18 patients,longest-followed patient still in remission beyond 10 months,no lymphodepletion; first multi-patient proofthe modality works, though numbers small and follow-up early•Phase I first-in-human CD8-tLNP study(7014): CD8-targeted lipid nanoparticle generating CD19 CAR-T in vivo via transient mRNA in r/r CD19+ B-cell lymphomao7 patients dosed (2 PR, 1 SD, 4 pending); CAR expression peaks at 4 to 6 hours with rapid near-complete B-cell depletion, no grade≥2 CRS and nolymphodepletion; in vivo proof-of-concept in lymphoma, but responses so far partial and expression transient •Phase I/II EVEREST-2, A2B694 arm (8579): A2 Bio's logic-gated mesothelinTmodCAR-T inadvanced HLA-A02 LOH solid tumors o13 patients across four dose levels, including the first reported CAR-T complete response in NSCLC; proof logic-gating can produce a solid-tumor response whilelimiting on-target/off-tumor toxicity KOL sentiment at ASCO 2026:Discussion centered oninMMyCAR, with excitement driven less by the response rate than by access, since an off-the-shelf product needing noapheresis, manufacturing, or lymphodepletion could reach the majority of myeloma patients who never get conventional CAR-T. KOLstempered this with c